Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a recently identified renal malignancy. Diagnosis of this rare subtype of renal tumour can be challenging for pathologists, and as ...such, any additional data would be helpful to improve diagnostic reliability. As imaging features of this new and rare sub-type have not yet been clearly described, the purpose of this study was to describe the main radiologic features on computed tomography (CT) and magnetic resonance imaging (MRI), based jointly on the literature and findings from a multi-institutional retrospective review of pathology and imaging databases. Using a combination of CT/MRI features, diagnosis of MTSCC could be suggested in many cases. A combination of slow enhancement with plateau on dynamic contrast-enhanced CT/MRI, intermediate to high T2 signal intensity contrasting with low apparent diffusion coefficient values on MRI appeared evocative of this diagnosis.
Key Points
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A slow enhancement with plateau is observed either on CT or MRI.
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High T2 signal components but low apparent coefficient diffusion are evocative.
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T2-weighted imaging features depend on the mucin components of the tumour.
Deficits in inhibitory function are assumed to underlie psychopathology in bipolar disorder (BD), especially in states of mania. A subdomain of inhibition, semantic inhibition (SI), referring to the ...suppression of irrelevant word meanings, may underlie formal thought disorder, such as flights of ideas. In the present study, we investigated SI in patients with BD during semantic ambiguity resolution using behavioral and event-related potential (ERP) measures. We presented 14 patients with BD with current manic, hypomanic, or mixed clinical states and 28 healthy controls sequentially with word triplets containing either a homonym (e.g., "organ") or a comparable unambiguous word (e.g., "piano"). Participants were instructed to make a decision whether or not the target word was related to the meaning field of the first two words. The inappropriate homonym meaning had to be inhibited to correctly perform the target decision. In addition to reaction times (RT) and error rates (ER), the N400 ERP component to the target, an electrophysiological index of semantic processing, was analyzed as measure of the amount of SI that had taken place. Analyses of the behavioral data revealed that BD patients exhibited an overall worse performance in terms of RT and ER. In the ERP data, we found differences in N400 amplitude to ambiguous and unambiguous conditions over the right hemisphere in patients with BD depending on target congruence: In incongruent trials, N400 amplitude was smaller in ambiguous than in unambiguous words. In congruent trials, in contrast, N400 amplitude was larger in ambiguous than in unambiguous words. Such ERP differences between ambiguous and unambiguous words were absent in controls. We conclude that N400 amplitude differences in the ambiguous and unambiguous conditions of the BD group may reflect insufficient suppression of irrelevant homonym meanings in the right hemisphere. Disturbed SI processes might contribute to formal thought disorder in BD.
Intracellular Stress Signaling Pathways Activated During Human Islet Preparation and Following Acute Cytokine Exposure
Saida Abdelli 1 ,
Jeff Ansite 2 ,
Raphael Roduit 1 ,
Tiziana Borsello 3 ,
Ippei ...Matsumoto 2 ,
Toshiya Sawada 2 ,
Nathalie Allaman-Pillet 1 ,
Hugues Henry 3 ,
Jacques S. Beckmann 1 ,
Bernhard J. Hering 2 and
Christophe Bonny 1
1 Service of Medical Genetics, Lausanne, Switzerland
2 Diabetes Institute for Immunology and Transplantation, University of Minnesota, Minneapolis, Minnesota
3 University Hospital Falaises, Lausanne, Switzerland
Address correspondence and reprint requests to Christophe Bonny, Service of Medical Genetics, 1011 Lausanne-CHUV, Switzerland.
E-mail: christophe.bonny{at}chuv.hospvd.ch . Or Bernhard J. Hering, Diabetes Institute for ImmunologyTransplantation, University of Minnesota, 420 Delaware St. SE, Mayo
Mailing Code no. 195, Minneapolis, MN 55455. E-mail: bhering{at}tumn.edu
Abstract
Pancreatic islet transplantation may successfully restore normoglycemia in type 1 diabetic patients. However, successful grafting
requires transplantation of a sufficient number of islets, usually requiring two or more donors. During the isolation process
and following clinical transplantation, islets are subjected to severe adverse conditions that impair survival and ultimately
contribute to graft failure. Here, we have mapped the major intracellular stress-signaling pathways that may mediate human
islet loss during isolation and following cytokine attack. We found that the isolation procedure potently recruits two pathways
consisting of |mitogen-activated protein kinase kinase (MKK)7 → Jun NH 2 -terminal kinase (JNK)/p38 → c- fos | and the |nuclear factor-κB (NF-κB) → iNOS| module. Cytokines activate the |NF-κB → iNOS| and |MKK4/MKK3/6 → JNK/p38| pathways
without recruitment of c- fos . Culturing the islets for 48 h after isolation allows for the activated pathways to return to background levels, with expression
of MKK7 becoming undetectable. These data indicate that isolation and cytokines recruit different death pathways. Therefore,
strategies might be rationally developed to avoid possible synergistic activation of these pathways in mediating islet loss
during isolation and following grafting.
DTT, dithiothreitol
EMSA, electrophoretic mobility shift assay
ERK, extracellular signal–regulated kinase
GST, glutathione S-transferase
IFNγ, γ-interferon
IκB, inhibitor of κB
IL-1β, interleukin-1β
iNOS, inducible nitric oxide synthase
JNK, c-Jun NH2-terminal kinase
MAPK, mitogen-activated protein kinase
MKK, MAPK kinase
NF-κB, nuclear factor-κB
PNF, primary graft nonfunction
TLM, two-layer cold storage method
TNFα, tumor necrosis factor-α
Footnotes
Accepted July 30, 2004.
Received February 6, 2004.
DIABETES
Here, we review the cerebrospinal fluid (CSF) candidate markers with regard to their clinical relevance as potential surrogates for disease activity, prognosis assessment, and predictors of treatment ...response. We searched different online databases such as MEDLINE and EMBASE for studies on schizophrenia and CSF. Initial studies on cerebrospinal fluid in patients with schizophrenia revealed increased brain–blood barrier permeability with elevated total protein content, increased CSF-to-serum ratio for albumin, and intrathecal production of immunoglobulins in subgroups of patients. Analyses of metabolites in CSF suggest alterations within glutamatergic neurotransmission as well as monoamine and cannabinoid metabolism. Decreased levels of brain-derived neurotrophic factor and nerve growth factor in CSF of first-episode patients with schizophrenia reported in recent studies point to a dysregulation of neuroprotective and neurodevelopmental processes. Still, these findings must be considered as non-specific. A more profound characterization of the particular psychopathological profiles, the investigation of patients in the prodromal phase or within the first episode of schizophrenia promoting longitudinal investigations, implementation of different approaches of proteomics, and rigorous adherence to standard procedures based on international CSF guidelines are necessary to improve the quality of CSF studies in schizophrenia, paving the way for identification of syndrome-specific biomarker candidates.
In acute myeloid leukemia (AML), internal tandem duplications (ITDs) of
are frequent mutations associated with unfavorable prognosis. At diagnosis, the
ITD status is routinely assessed by fragment ...analysis, providing information about the length but not the position and sequence of the ITD. To overcome this limitation, we performed cDNA-based high-throughput amplicon sequencing (HTAS) in 250
ITD positive AML patients, treated on German AML Cooperative Group (AMLCG) trials.
ITD status determined by routine diagnostics was confirmed by HTAS in 242 out of 250 patients (97%). The total number of ITDs detected by HTAS was higher than in routine diagnostics (
= 312 vs.
= 274). In particular, HTAS detected a higher number of ITDs per patient compared to fragment analysis, indicating higher sensitivity for subclonal ITDs. Patients with more than one ITD according to HTAS had a significantly shorter overall and relapse free survival. There was a close correlation between
ITD mRNA levels in fragment analysis and variant allele frequency in HTAS. However, the abundance of long ITDs (≥75nt) was underestimated by HTAS, as the size of the ITD affected the mappability of the corresponding sequence reads. In summary, this study demonstrates that HTAS is a feasible approach for
ITD detection in AML patients, delivering length, position, sequence and mutational burden of this alteration in a single assay with high sensitivity. Our findings provide insights into the clonal architecture of
ITD positive AML and have clinical implications.
Oxidation of wine while in contact with oak wood is a well-known fact and recognized as an important process in wine ageing. The slow and continuous diffusion of oxygen from the oak wood entrapped in ...its porosity occurs and encourages the reactions usually related with wine aging. In this work, oxygen sensitive particles were used to study the oxygen dynamics from different anatomical regions of the oak wood and simultaneously the oxygen increasement because of the deoxygenation of the wood and the oxygen depletion due to its consumption by the tannins and other compounds released from the wood. To this end, core-shell-type PSPVP nanoparticles stained with Macrolex Fluorescence Yellow and Pt-TFPP were employed as reference and oxygen-sensitive particles respectively. Moreover, a Guppy Pro RGB camera was employed to monitor the particles performing ratiometric oxygen imaging, using the green and red channels to acquire the light emitted from the reference and the oxygen-sensitive particles respectively. Because the volume of nanosensors corresponding to each surface unit is very different from that of the wood region, different exposure times were chosen to obtain the images at each of the times. The results show the wood degassing process during the first minutes of the experiment, the oxygen release from different structural elements of the wood, its consumption by the released compounds from wood and the diffusion of the oxygen through the model wine.
Abstract Objective To examine the appropriateness of visual memory tests as an identification method for right mesial temporal lobe dysfunctions in an epilepsy patient group and to study the ...relationship and possible overlap with non-memory cognitive domains and demographic variables. Methods Eighty preoperative candidates with mesial temporal lobe epilepsy (TLE) were examined using the “Corsi Block-Tapping Test”, “Diagnosticum für Cerebralschädigung” (DCS), the path subtest of the “Verbaler und Visueller Merkfähigkeitstest” (VVM), and the Rey-Osterrieth Complex Figure Test (ROCF). Factorial analyses were performed on raw scores to determine the effect of epilepsy–related variables, interictal epileptiform discharges (IEDs) and presence of cortical dysgenesis, on visual and verbal memory parameters. Sensitivity, specificity and Receiver Operating Characteristic (ROC) curves were calculated based on normative data. Furthermore, Spearman correlations between memory and non-memory cognitive tasks were performed. Results The scores for test sensitivity and specificity and the ROC curves illustrate the tests' poor capacity to lateralize the functional deficit zone even when epilepsy–related factors, such as cortical dysgenesis or presence of contralateral IEDs were controlled. Significant correlations were found between the visual memory measures and nonverbal reasoning, processing speed, attentional flexibility, and visual planning. Conclusion These neuropsychological tests are not sensitive enough to lateralize the epileptogenic focus in temporal lobe epilepsy patients since in addition to learning and consolidation processes, they measure additional cognitive domains. These results have implications for clinical neuropsychologists, in terms of test choice and the interpretation in the context of presurgical diagnostics.
A series of polystyrene- and poly(methyl methacrylate)-dithioesters was subjected to aminolysis under ambient atmospheric conditions,
i.e.
, in the presence of oxygen. Polymer disulfide coupling by ...oxidation occurred within tens of minutes and the yield of disulfide-coupled polymer increased with decreasing polymer molar mass. Oxidation of thiolates is usually an unwanted side reaction, here it is employed to obtain exclusively polymeric mixed disulfides through
in situ
aminolysis/functionalization in the presence of a thiol. The
in situ
aminolysis/functionalization in the presence of a disulfide, Ellman's reagent or polymer disulfide, resulted in the exclusive formation of polymer-dithionitrobenzoic acid, which can be further reacted with a thiol to exchange the terminal functionality, or block copolymer with dynamic disulfide linker, respectively.
Efficient exchange of the polymer-dithioester end group by aminolysis/functionalization with thiol or disulfide under ambient atmospheric conditions.
Abstract Individuals with autism who show high abilities are called savants. Whereas in their brains a disconnection in and between neural networks has been identified, savantism is yet poorly ...understood. Focusing on astrocyte domain organization, it is hypothesized that local astrocyte mega-organizations may be responsible for exerting high capabilities in brains of autistic savants. Astrocytes, the dominant glial cell type, modulate synaptic information transmission. Each astrocyte is organized in non-overlapping domains. Formally, each astrocyte contacting n -neurons with m -synapses via its processes generates dynamic domains of synaptic interactions based on qualitative computation criteria, and hereby it structures neuronal information processing. If the number of processes is genetically significantly increased, these astrocytes operate in a mega-domain with a higher complexitiy of computation. From this model savant abilities are deduced.
Abstract Background Although abiraterone acetate (abiraterone) has proven efficacy in two randomised phase 3 trials in metastatic castration-resistant prostate cancer (mCRPC), patients who had an ...Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2 were either excluded or under-represented in these trials. Objective To compare outcomes in ECOG PS 0–1 and ≥2 in mCRPC patients treated with abiraterone. Design, setting, and participants Cancer registries from three Canadian centres were used to retrospectively identify mCRPC patients (postdocetaxel and docetaxel-naïve) treated with abiraterone. ECOG PS, clinicopathologic characteristics, prostate-specific antigen (PSA) response, and survival data were collected. Outcome measurements and statistical analysis Survival outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards modelling was used to examine the effect of clinicopathologic characteristics on overall survival (OS) and time to PSA progression. Results and limitations A total of 519 patients were identified; 61% ( n = 318) and 39% ( n = 201) were ECOG PS 0–1 and ≥2, respectively. ECOG PS 0–1 patients were significantly more likely than PS ≥2 patients to achieve a PSA decline ≥50% from baseline (45% vs 32%; p = 0.003, Fisher exact test) and had significantly longer median time to PSA progression (5.2 mo vs 4.1 mo; p = 0.023), median treatment duration (7.4 mo vs 4.5 mo; p < 0.001), and median OS (20.0 mo vs 9.1 mo; p < 0.001). On multivariate analysis, ECOG PS was a significant factor for OS ( p < 0.001), time to PSA progression ( p = 0.043), and PSA decline ( p = 0.002). Potential limitations include the retrospective study design and subjective nature of ECOG PS classification. Conclusions ECOG PS ≥2 mCRPC patients treated with abiraterone have inferior outcomes compared with ECOG 0–1 patients, especially in regard to OS. These data indicate that early initiation of abiraterone prior to a decline in PS may be warranted. Patient summary We found that advanced prostate cancer patients who have worse performance status (PS) derive less benefit from abiraterone, indicating that earlier treatment before PS declines could improve outcomes.
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